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Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease
Open accessAbstract
Although there have been major advances in the treatment of rheumatoid arthritis with the advent of biological agents, the mechanisms that drive cytokine production and sustain disease chronicity remain unknown. Tenascin-C (encoded by Tnc) is an extracellular matrix glycoprotein specifically expressed at areas of inflammation and tissue damage in inflamed rheumatoid joints. Here we show that mice that do not express tenascin-C show rapid resolution of acute joint inflammation and are protected from erosive arthritis. Intra-articular injection of tenascin-C promotes joint inflammation in vivo in mice, and addition of exogenous tenascin-C induces cytokine synthesis in explant cultures from inflamed synovia of individuals with rheumatoid arthritis. Moreover, in human macrophages and fibroblasts from synovia of individuals with rheumatoid arthritis, tenascin-C induces synthesis of proinflammatory cytokines via activation of Toll-like receptor 4 (TLR4). Thus, we have identified tenascin-C as a novel endogenous activator of TLR4-mediated immunity that mediates persistent synovial inflammation and tissue destruction in arthritic joint disease.
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Cites
DAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794
Decoding the Patterns of Self and Nonself by the Innate Immune System
Medzhitov, R., & Janeway, C. A. (2002) · Science · doi:10.1126/science.1068883 · Cited by 2,154
Schaefer, L., Babelova, A., Kiss, E., Hausser, H.-J., Baliova, M., Krzyzankova, M., Marsche, G., Young, M. F., Mihalik, D., Götte, M., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23755 · Cited by 850
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Extracellular matrix structure
Theocharis, A. D., Skandalis, S. S., Gialeli, C., & Karamanos, N. K. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.11.001 · Cited by 2,598
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672
Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment
Chanmee, T., Ontong, P., Konno, K., & Itano, N. (2014) · Cancers · doi:10.3390/cancers6031670 · Cited by 1,538
Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis
Robinson, W. H., Lepus, C. M., Wang, Q., Raghu, H., Mao, R., Lindstrom, T. M., & Sokolove, J. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.136 · Cited by 1,438
The role of synovitis in osteoarthritis pathogenesis
Scanzello, C. R., & Goldring, S. R. (2012) · Bone · doi:10.1016/j.bone.2012.02.012 · Cited by 1,302
Fibroblasts in fibrosis: novel roles and mediators
Kendall, R. T., & Feghali-Bostwick, C. A. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00123 · Cited by 1,082
Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations
Sokolove, J., & Lepus, C. M. (2013) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x12467868 · Cited by 1,100
Adipokine dysregulation and adipose tissue inflammation in human obesity
Unamuno, X., Gómez‐Ambrosi, J., Rodríguez, A., Becerril, S., Frühbeck, G., & Catalán, V. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.12997 · Cited by 610
The role of tenascin-C in tissue injury and tumorigenesis
Midwood, K. S., & Orend, G. (2009) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-009-0075-1 · Cited by 438
Self-citationMidwood, K. S., Chiquet, M., Tucker, R. P., & Orend, G. (2016) · Journal of Cell Science · doi:10.1242/jcs.190546 · Cited by 429
Self-citationTLR agonists: our best frenemy in cancer immunotherapy
Kaczanowska, S., Joseph, A. M., & Davila, E. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1012501 · Cited by 339
The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis
Desai, O., Winkler, J., Minasyan, M., & Herzog, E. L. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00043 · Cited by 314
DAMPs as mediators of sterile inflammation in aging-related pathologies
Feldman, N., Rotter-Maskowitz, A., & Okun, E. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.003 · Cited by 283
Danger-associated molecular patterns in Alzheimer’s disease
Venegas, C., & Heneka, M. T. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0416-204r · Cited by 236
Tenascin C in metastasis: A view from the invasive front
Lowy, C. M., & Oskarsson, T. (2015) · Cell Adhesion & Migration · doi:10.1080/19336918.2015.1008331 · Cited by 178
Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment
McQuitty, C. E., Williams, R., Chokshi, S., & Urbani, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.574276 · Cited by 146
Extracellular Matrix Remodeling and Stiffening Modulate Tumor Phenotype and Treatment Response
Leight, J. L., Drain, A. P., & Weaver, V. M. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-034431 · Cited by 131
Lampropoulou, V., Calderon‐Gomez, E., Roch, T., Neves, P., Shen, P., Stervbo, U., Boudinot, P., Anderton, S. M., & Fillatreau, S. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00855.x · Cited by 130
Hongu, T., Pein, M., Insua-Rodríguez, J., Gutjahr, E., Mattavelli, G., Meier, J., Decker, K., Descot, A., Bozza, M., Harbottle, R., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00353-6 · Cited by 118
Rogier, R., Ederveen, T. H. A., Boekhorst, J., Wopereis, H., Scher, J. U., Manasson, J., Frambach, S. J. C. M., Knol, J., Garssen, J., van der Kraan, P. M., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0278-2 · Cited by 98
PAI1 mediates fibroblast-mast cell interactions in skin fibrosis
Pincha, N., Hajam, E. Y., Badarinath, K., Batta, S. P. R., Masudi, T., Dey, R., Andreasen, P., Kawakami, T., Samuel, R., George, R., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99088 · Cited by 70
Regulation of IL-6 secretion by astrocytes via TLR4 in the fragile X mouse model.
Krasovska, V., & Doering, L. C. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00272 · Cited by 47
TNC‑targeted CAR‑macrophage therapy alleviates liver fibrosis in mice
Chen, K., Lin, Z., Chen, L., Zhou, Y., Zhang, W., Wan, H., Huo, Y., Fu, Q., Gao, Z., Cheng, H., et al. (2025) · Military Medical Research · doi:10.1186/s40779-025-00667-3 · Cited by 11
Metadata
- Authors
- Midwood, K., Sacre, S., Piccinini, A. M., Inglis, J., Trebaul, A., Chan, E., Drexler, S., Sofat, N., Kashiwagi, M., Orend, G., Brennan, F., & Foxwell, B.
- Venue
- Nature Medicine
- Published
- 2009-06-28
- Volume
- 15
- Issue
- 7
- Pages
- 774-780
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2049907045
- Cited by
- 703
- References
- 3
- FWCI
- 31.49
- Type
- journal article
- Language
- en
- Open access
- green
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